Nicotinamide Riboside (NR): Benefits and Side Effects
Nicotinamide riboside (NR) is part of the B3 vitamin family. Like other forms of vitamin B3, nicotinamide riboside gets converted into nicotinamide adenine dinucleotide (NAD+), a coenzyme essential for life. For this reason, it is often called a NAD+ precursor because it is part of the series of chemical steps that are required to create NAD+.
What does nicotinamide riboside do?
An important function of NR is to act as an intermediary, convert itself into NAD+, and provide fuel to our cells so that they can keep working. NR is one of four ways in which our body can create NAD+.
This chart shows the various pathways through which NAD+ is created, including the steps that NR goes through from being consumed in food or taken as a supplement.
NR is commonly marketed as an NAD+ booster or anti-aging supplement. Indeed, there is some evidence that NR can increase NAD+ levels in humans and not just mice [1]. Tru Niagen and Elysium Basis are two of the most common suppliers.
What is NAD+?
NAD+ is a critical coenzyme found in all living cells and is essential to life. It is a dinucleotide, which means that it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine base, and the other contains nicotinamide. NAD+ is one of the most versatile molecules in the body, and is an area of intense focus for aging research.
NAD+ acts as fuel for many key biological processes:
- Converting nutrients into energy
- Repairing DNA damage
- Fortifying cells’ defense systems
- Regulating the circadian rhythm
Unfortunately, as we age, the levels of NAD+ decline leading to increasingly less energy for cellular functions. This can contribute to the development of various age-related diseases such as diabetes,
You can learn more about NAD+ by clicking on this topic box:
Nicotinamide riboside in food
NR is present in beer, yeast, and cows’ milk, but before you rush out to grab a pint or two of your favorite beer, do bear in mind it only contains a trace amount of NR [2]. It should go without saying that we do not recommend excessive beer consumption as a good approach to getting more NR into your diet or for longevity.
Nicotinamide riboside benefits
The majority of research on NR has been conducted on animals rather than via human clinical studies. Because of this, there are no firm conclusions regarding its effectiveness in humans, especially in the context of aging.
However, there may be some potential benefits of NR, though more human studies really should be done, especially comparisons between it and other NAD+ precursors like NMN and Niacin. In general, the human studies that have been conducted offer evidence that NR provides benefits to various aspects of health.
Nicotinamide riboside may support heart health
The leading cause of death in the world is heart disease, and aging is a leading risk factor for it. Aging causes our blood vessels to become stiffer and less flexible. This causes our blood pressure to rise and forces the heart to work harder to pump the blood around our body. Over time, high blood pressure raises the risk of heart disease and could have fatal consequences.
In a human study, the administration of nicotinamide riboside reduced aortic stiffness and blood pressure in middle-aged and older adults [3].
Another human study showed that NR reduced systolic blood pressure and aortic stiffness, and it increased NAD+ associated metabolites, including adenosine and adenosine triphosphate [4]. This supports the idea that NR does increase systemic NAD+ levels and other molecules associated with the regulation of energy production and metabolism.
While there is significant interest in the potential of NR for treating cardiovascular disease, more research is needed.
Nicotinamide riboside may help with weight control
One study found that nicotinamide riboside supplementation altered body composition and skeletal muscle acetylcarnitine concentrations in otherwise healthy obese humans [5]. The study saw healthy overweight or obese men and women take one gram a day for a 6-week period.
It was found that markers of NAD+ synthesis were increased in skeletal muscle when compared to the control group. Acetylcarnitine metabolism was also shown to be increased by the presence of NR in skeletal muscle tissue. Acetylcarnitine metabolism has been linked with metabolic flexibility and improved metabolic health.
However, the reason why NR influences metabolism in this way is still unclear. NR also appeared to induce minor changes in body composition and sleeping metabolic rate in the participants.
This study showed absolutely no effect on insulin sensitivity, mitochondrial function, hepatic and intramyocellular lipid accumulation, cardiac energy status, cardiac ejection fraction, ambulatory blood pressure, plasma markers of inflammation, or energy metabolism.
These mixed results are once again another indication that much more research is needed around NR before it is properly understood.
More mixed results for nicotinamide riboside
A small 2019 human study found no clinical benefit to supplementation with the drug [6]. During the study, the impact of the drug on a few markers of disease and frailty was analyzed. Grip strength and muscle blood flow and metabolism saw no improvement following NR.
However, meNAM, a protein thought to be increased in type 2 diabetes and insulin resistance, did see a significant increase. However, the study found no impact on type 2 diabetes or insulin resistance, so it is unclear what these changes mean.
Finally, the study did show that levels of a protein called NAAD, a biomarker associated with NAD+ boosting supplements, was significantly increased in muscle. The study also reported an increase of NAM excretion products – potentially the result of the target muscle tissues already having enough NAD+ before the study began.
Nicotinamide riboside side effects
No serious adverse effects have been reported in human studies, though most of the studies so far have been short in duration and low in participant numbers. The need for larger scale and more robust human studies is critical if NR is to be properly evaluated.
To date, some people have reported mild to moderate side effects, including nausea, fatigue, headaches, diarrhea, stomach upset and indigestion. While that seems to suggest NR is likely safe, the lack of large scale long-term studies means that this cannot be confirmed.
As always, if you do decide to take a NR supplement and experience any adverse effects, you should cease taking it immediately and consult your doctor.
Disclaimer
This article is only a very brief summary. It is not intended as an exhaustive guide and is based on the interpretation of research data, which is speculative by nature. This article is not a substitute for consulting your physician about which supplements may or may not be right for you. We do not endorse supplement use or any product or supplement vendor, and all discussion here is for scientific interest.
Literature
[1] Trammell, S. A., Schmidt, M. S., Weidemann, B. J., Redpath, P., Jaksch, F., Dellinger, R. W., … & Brenner, C. (2016). Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nature communications, 7(1), 1-14.
[2] Lee, H. J., Hong, Y. S., Jun, W., & Yang, S. J. (2015). Nicotinamide riboside ameliorates hepatic metaflammation by modulating NLRP3 inflammasome in a rodent model of type 2 diabetes. Journal of medicinal food, 18(11), 1207-1213.
[3] Martens, C., Denman, B., Mazzo, M., Armstrong, M., Reisdorph, N., McQueen, M., … & Seals, D. (2017). NAA1 NICOTINAMIDE RIBOSIDE SUPPLEMENTATION REDUCES AORTIC STIFFNESS AND BLOOD PRESSURE IN MIDDLE-AGED AND OLDER ADULTS. Artery Research, 20(C), 49-49.
[4] Martens, C. R., Denman, B. A., Mazzo, M. R., Armstrong, M. L., Reisdorph, N., McQueen, M. B., … & Seals, D. R. (2018). Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nature communications, 9(1), 1-11.
[5] Remie, C. M., Roumans, K. H., Moonen, M. P., Connell, N. J., Havekes, B., Mevenkamp, J., … & Schrauwen, P. (2020). Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans. The American journal of clinical nutrition, 112(2), 413-426.
[6] Elhassan, Y. S., Kluckova, K., Fletcher, R. S., Schmidt, M. S., Garten, A., Doig, C. L., Cartwright, D. M., Oakey, L., Burley, C. V., Jenkinson, N., Wilson, M., Lucas, S., Akerman, I., Seabright, A., Lai, Y. C., Tennant, D. A., Nightingale, P., Wallis, G. A., Manolopoulos, K. N., Brenner, C., … Lavery, G. G. (2019). Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures. Cell reports, 28(7), 1717–1728.e6. https://doi.org/10.1016/j.celrep.2019.07.043
[7] Trammell, S. A., Schmidt, M. S., Weidemann, B. J., Redpath, P., Jaksch, F., Dellinger, R. W., … & Brenner, C. (2016). Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nature communications, 7, 12948.
